Genomes and Genes
Gene Symbol: Prf1
Description: perforin 1 (pore forming protein)
Alias: Pfn, Pfp, Prf-1, cytolysin, lymphocyte pore-forming protein, perforin-1, pore forming protein
Publications128 found, 100 shown here
- NK cell-mediated immunopathology during an acute viral infection of the CNSMohammed Alsharifi
Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, Australia
Eur J Immunol 36:887-96. 2006..This is the first study illustrating an NK cell-mediated immunopathological outcome to an acute viral infection...
- Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforinJ Pardo
Metschnikoff Laboratory, Max Planck Institut for Immunbiology, Stubeweg 51, Freiburg, Germany
Cell Death Differ 14:1768-79. 2007..The data suggest that activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues...
- Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cellsShayna E A Street
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre Peter Mac, 8006, Victoria, Australia
J Exp Med 199:879-84. 2004..These results reflect a critical role for NK cells and gammadeltaTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition...
- The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in miceM B Baker
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101, USA
J Exp Med 183:2645-56. 1996..In addition, perforin-mediated anti-recipient cytotoxicity appears to play an important role in the kinetics of GVHD pathophysiology, but is not required for GVHD-associated tissue damage...
- Cutting edge: granzymes A and B are not essential for perforin-mediated tumor rejectionMark J Smyth
Cancer Immunology Program, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia
J Immunol 171:515-8. 2003....
- Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient miceD Kagi
Department of Pathology, University of Zurich, Switzerland
Nature 369:31-7. 1994..The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis...
- TRAIL identifies immature natural killer cells in newborn mice and adult mouse liverKazuyoshi Takeda
Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bukyou ku, Tokyo 113 8421, Japan
Blood 105:2082-9. 2005..This study is the first to describe the concomitant maturation of NK cell effector function with surface phenotype in vivo and implies an important defense role for NK cell TRAIL in the developing immune system...
- Decreased tumor surveillance in perforin-deficient miceM E van den Broek
Institute of Experimental Immunology, University of Zurich, Switzerland
J Exp Med 184:1781-90. 1996....
- Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAsTodd A Fehniger
Division of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA
Immunity 26:798-811. 2007..These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation...
- Perforin is a major contributor to NK cell control of tumor metastasisM J Smyth
Cellular Immunity Laboratory, Austin Research Institute, Heidelberg, Victoria, Australia
J Immunol 162:6658-62. 1999..Depletion of NK subsets resulted in greater numbers of metastases than observed in perforin-deficient mice, suggesting that perforin-independent effector functions of NK cells may also contribute to protection from tumor metastasis...
- Absence of perforin expression confers axonal protection despite demyelinationCharles L Howe
Department of Neuroscience, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA
Neurobiol Dis 25:354-9. 2007..We conclude that perforin-dependent effector cells such as cytotoxic T cells, gammadelta T cells, and natural killer cells may play a role in axon damage that is dependent upon but separable from demyelination...
- West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protectionJames D Brien
Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
J Immunol 181:8568-75. 2008..These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease...
- Differential tumor surveillance by natural killer (NK) and NKT cellsM J Smyth
Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
J Exp Med 191:661-8. 2000..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
- Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gammaV P Badovinac
Department of Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Science 290:1354-8. 2000..Thus, perforin and IFN-gamma regulate distinct elements of CD8+ T cell homeostasis independently of their role as antimicrobial effector molecules...
- Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasisS E Street
Cancer Immunology, Peter MacCallum Cancer Institute, Victoria, Australia
Blood 97:192-7. 2001Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity...
- IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gammaHak Ling Ma
Wyeth Research, Cambridge, MA 02140, USA
J Immunol 171:608-15. 2003..We conclude that IL-21 immunotherapy warrants clinical evaluation as a potential treatment for cancer...
- Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient miceErika Cretney
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A Beckett Street, East Melbourne, 8006 Victoria, Australia
J Immunol 168:1356-61. 2002..TRAIL gene-targeted mice were also more sensitive to the chemical carcinogen methylcholanthrene. These results substantiated TRAIL as an important natural effector molecule used in the host defense against transformed cells...
- Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liverJoy Loh
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Virol 79:661-7. 2005..of the acute phase of murine cytomegalovirus (MCMV) infection and have been reported to utilize perforin (Pfp)- and gamma interferon (IFN-gamma)-dependent effector mechanisms in an organ-specific manner to regulate MCMV ..
- Suppression of lymphoma and epithelial malignancies effected by interferon gammaShayna E A Street
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia
J Exp Med 196:129-34. 2002..we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-gamma and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF)...
- Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cellsC H Tay
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA
J Virol 71:267-75. 1997..These results may explain why the Cmv-lr locus, which maps closely to genes regulating NK cell cytotoxic function, confers an NK cell-dependent resistance to MCMV infection in the spleen but not in the liver...
- An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorderMichael B Jordan
Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, USA
Blood 104:735-43. 2004..These studies provide insight into the pathophysiology of HLH, and provide new targets for specific therapeutic intervention in this fatal disorder...
- Perforin-dependent neurologic injury in a viral model of multiple sclerosisP D Murray
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
J Neurosci 18:7306-14. 1998..These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination...
- Demyelinated axons and motor function are protected by genetic deletion of perforin in a mouse model of multiple sclerosisChandra Deb
Departments of Neurology, Mayo Clinic, Rochester, Minnesota
J Neuropathol Exp Neurol 68:1037-48. 2009..These results suggest that perforin is a key mediator of axon injury and lend additional support to the hypothesis that CD8 T cells are primarily responsible for axon damage in multiple sclerosis...
- In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cellsM M Simon
Max Planck Institut für Immunbiology, Freiburg, Germany
J Exp Med 186:1781-6. 1997..This suggests that gzmA and B are critical for Tc/NK granule- mediated nucleolysis, with gzmB being the main contributor, while target cell lysis is due solely to perforin and independent of both proteases...
- Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytesH Kojima
Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan
Immunity 1:357-64. 1994..These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis...
- Immune function in mice lacking the perforin geneC M Walsh
Department of Biology, University of California, Los Angeles 90024
Proc Natl Acad Sci U S A 91:10854-8. 1994..We conclude that perforin-less -/- mice retain and express the Fas lytic pathway as expressed in vitro but that this pathway is insufficient to clear an LCMV infection in vivo...
- Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathwaysB Lowin
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
Nature 370:650-2. 1994..Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand-receptor interaction...
- Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicityD Kagi
Department of Pathology, University of Zurich, Switzerland
Science 265:528-30. 1994..All cytotoxicity observed was due to either of these mechanisms, and no third mechanism was detected. Thus, the perforin- and Fas-based mechanisms may account for all T cell-mediated cytotoxicity in short-term in vitro assays...
- Genomic organization of the mouse pore-forming protein (perforin) gene and localization to chromosome 10. Similarities to and differences from C9J A Trapani
Laboratory of Human Immunogenetics, Memorial Sloan Kettering Cancer Center, New York, New York 10021
J Exp Med 171:545-57. 1990Genomic clones encompassing the entire coding region of the mouse lymphocyte pore-forming protein gene (Pfp) have been isolated and used to determine its intron-exon organization...
- Reduced incidence and delayed onset of diabetes in perforin-deficient nonobese diabetic miceD Kagi
Ontario Cancer Institute, Toronto M5G2M9, Canada
J Exp Med 186:989-97. 1997..However, in the absence of perforin chronic inflammation of the islets can lead to diabetogenic beta cell loss by less efficient secondary effector mechanisms...
- IL-21 induces the functional maturation of murine NK cellsJason Brady
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
J Immunol 172:2048-58. 2004..These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance...
- Perforin and granzymes have distinct roles in defensive immunity and immunopathologySerani L H van Dommelen
Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Western Australia, Australia
Immunity 25:835-48. 2006..Here we showed that perforin (Prf1) and granzymes (Gzms) have distinct roles in defensive immunity and immunopathology in a well-established model of ..
- A null mutation in the perforin gene impairs cytolytic T lymphocyte- and natural killer cell-mediated cytotoxicityB Lowin
Institute of Biochemistry, University of Lausanne, Switzerland
Proc Natl Acad Sci U S A 91:11571-5. 1994..We conclude that perforin is a crucial effector molecule in T cell- and NK cell-mediated cytolysis. However, alternative perforin-independent lytic mechanisms also exist...
- Murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infectionL Riera
Department of Public Health and Microbiology, Medical School, Torino, Italy
Eur J Immunol 30:1350-5. 2000....
- Myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas- and Fas ligand-deficient lpr and gld miceU Malipiero
Department of Neurosurgery, University Hospital Zurich, Switzerland
Eur J Immunol 27:3151-60. 1997..Unlike oligodendrocytes, astrocytes were killed by FasL in vitro. It remains to be established whether this latter finding explains the different disease course of lpr and gld mice compared to wild-type and perforin knockout mice...
- Perforin protects against autoimmunity in lupus-prone miceS L Peng
Department of Biology, Yale University, New Haven, CT 06510, USA
J Immunol 160:652-60. 1998....
- Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytesA Mullbacher
Division of Immunology, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
Proc Natl Acad Sci U S A 96:13950-5. 1999..These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens...
- Perforin-dependent cytolytic responses in beta2-microglobulin-deficient miceM J Smyth
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Studley Road, Heidelberg, Victoria, 3084, Australia
Cell Immunol 196:51-9. 1999..Dependence on perforin function was demonstrated for the cytotoxicity of these effectors in vitro and for the ability of these effectors to reject a variety of tumors in vivo...
- Perforin/Fas-ligand double deficiency is associated with macrophage expansion and severe pancreatitisJ Spielman
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33136, USA
J Immunol 161:7063-70. 1998..These studies demonstrate a novel role for perforin in homeostatic regulation of the immune response...
- Perforin-expressing cytotoxic cells contribute to chronic cardiomyopathy in Trypanosoma cruzi infectionJaline Coutinho Silverio
Laboratório de Biologia das Interações, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
Int J Exp Pathol 91:72-86. 2010..cruzi strain. This protocol led to acute phase survival in both wild-type and perforin null (pfp(-/-)) mice lineages...
- Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activityRobert Zeiser
Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Blood 110:4588-98. 2007....
- Cytotoxic T lymphocytes overcome Bcl-2 inhibition: target cells contribute to their own demiseIng Swie Goping
Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
Blood 111:2142-51. 2008..This ensures that CTLs can eliminate those target cells that have compromised apoptotic potential due to overexpression of Bcl-2...
- Prolonged production of TNF-alpha exacerbates illness during respiratory syncytial virus infectionJohn A Rutigliano
Vaccine Research Center National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 173:3408-17. 2004..In addition, the revelation that TNF-alpha is the principal mediator of RSV-induced illness means that administration of TNF receptor antagonists, in combination with antiviral therapy, may be an effective method to treat RSV infections...
- Interleukin-15/interleukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cellsMathieu Epardaud
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
Cancer Res 68:2972-83. 2008....
- Transmission of Toxoplasma gondii from infected dendritic cells to natural killer cellsCatrine M Persson
Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, F59, Karolinska University Hospital Huddinge, Stockholm, Sweden
Infect Immun 77:970-6. 2009..These results suggest that rapid transfer of T. gondii from infected DC to effector NK cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection...
- The role of TNF-TNFR2 interactions in generation of CTL responses and clearance of hepatic adenovirus infectionMichel I Kafrouni
Department of Internal Medicine, Divison of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, 75390 9151, USA
J Leukoc Biol 74:564-71. 2003..These findings indicate that TNF/TNFR2 interactions facilitate generation of FasL-dependent CTL effector pathways that play an important role in in vivo antiviral-immune responses in the liver...
- Up-regulation of Fas (CD95) expression in tumour cells in vivoNaama Peshes-Yaloz
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Immunology 120:502-11. 2007..Our model is that host lymphoid cells in response to a tumour increase NO synthesis, which in turn causes enhanced Fas expression in the tumour...
- Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivoHelen M A Simkins
Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand
J Leukoc Biol 89:753-62. 2011..Thus, iNKT cells regulate the survival of CD8(+) DCs through a mechanism that does not appear to involve direct cell killing...
- IFN-gamma-producing dendritic cells are important for priming of gut intraepithelial lymphocyte response against intracellular parasitic infectionMagali M Moretto
Department of Microbiology, Parasitology and Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
J Immunol 179:2485-92. 2007..To our knowledge, this report is the first demonstrating a role for IFN-gamma-producing DC from Peyer's patches in the development of Ag-specific IEL population and their trafficking to the gut epithelium...
- CD8 T cell-initiated vascular endothelial growth factor expression promotes central nervous system vascular permeability under neuroinflammatory conditionsGeorgette L Suidan
Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
J Immunol 184:1031-40. 2010....
- 2B4 inhibits NK-cell fratricideRuth T Taniguchi
University of Chicago Department of Pathology, Committee on Immunology, Chicago, IL 60637, USA
Blood 110:2020-3. 2007..We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal...
- IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasisMichele W L Teng
Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia
Proc Natl Acad Sci U S A 107:8328-33. 2010..Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A...
- In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemiaJaebok Choi
Division of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA
Blood 116:129-39. 2010..Their suppressor function is dependent on direct contact, partially dependent on perforin 1 (Prf1), but independent of granzyme B (GzmB), and surprisingly, Foxp3...
- Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potencyGerhard Wingender
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA
J Immunol 185:2721-9. 2010..Therefore, unlike NK cells, which rely mostly on perforin/granzyme-mediated mechanisms, the Ag-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway...
- IL-21 enhances tumor rejection through a NKG2D-dependent mechanismRayna Takaki
Department of Microbiology and Immunology, Biomedical Sciences Graduate Program and The Cancer Research Institute, University of California, San Francisco, CA 94143, USA
J Immunol 175:2167-73. 2005..Collectively, these findings suggest that IL-21 therapy may work optimally against tumors that can elicit a NKG2D-mediated immune response...
- Perforin deficiency attenuates collagen-induced arthritisKristin Bauer
Institute of Immunology, University of Rostock, Rostock, Germany
Arthritis Res Ther 7:R877-84. 2005..In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells, for the pathogenesis of ..
- Solid tumors "melt" from the inside after successful CD8 T cell attackUlrike Blohm
Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany
Eur J Immunol 36:468-77. 2006..Thus, our data also imply that adoptive transfer of tumor-specific CD8 T cells might synergize with radiation therapy or chemotherapy in the elimination of solid tumors in vivo...
- Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-gamma but requires TNF-alphaD W White
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City 52242, USA
J Immunol 160:898-905. 1998..These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-gamma, but requires TNF-alpha...
- Deficiency of merosin in dystrophic dy mice and genetic linkage of laminin M chain gene to dy locusY Sunada
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242
J Biol Chem 269:13729-32. 1994....
- Regulation of perforin gene expression in a T cell hybrid with inducible cytolytic activityJ A Garcia-Sanz
Department of Microbiology and Immunology, University of Miami, School of Medicine
Eur J Immunol 23:1877-83. 1993..In addition, we confirm the existence of two types of mouse perforin mRNA that differ in their 5' untranslated regions, and show evidence that both mRNA are translated in vivo with similar efficiencies...
- Genetic mapping of gene encoding the farnesoid receptor, Fxr, to mouse Chromosome 10C A Kozak
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA
Mamm Genome 7:164-5. 1996
- Cutting edge: perforin down-regulates CD4 and CD8 T cell-mediated immune responses to a transplanted organAnirban Bose
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
J Immunol 170:1611-4. 2003..In contrast, perforin did not influence T cell proliferation. Therefore, perforin is an essential immunoregulatory molecule that may be required for the induction of transplantation tolerance...
- Cytokine deprivation of naive CD8+ T cells promotes minimal cell cycling but maximal cytokine synthesis and autonomous proliferation subsequently: a mechanism of self-regulationS Sad
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario
J Immunol 163:2443-51. 1999..These results suggest that the presence of excessive IL-2 during the activation of naive CD8+ T cells, while promoting cell cycling initially, may compromise long-term immunity...
- m144, a murine cytomegalovirus (MCMV)-encoded major histocompatibility complex class I homologue, confers tumor resistance to natural killer cell-mediated rejectionE Cretney
Cellular Immunity Laboratory, The Austin Research Institute, Melbourne, Victoria, Australia
J Exp Med 190:435-44. 1999....
- Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified miceM E Rottenberg
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden
J Immunol 162:2829-36. 1999..pneumoniae. The higher sensitivity of IFN-gammaR-/- mice to C. pneumoniae compared with that of SCID or recombination-activating gene-1-/- mice suggested a relevant protective role of IFN-gamma-dependent innate mechanisms of protection...
- Relative perforin- and Fas-mediated lysis in T1 and T2 CD8 effector populationsL L Carter
Department of Molecular Pathology, University of California San Diego Cancer Center, La Jolla 92093, USA
J Immunol 155:1028-31. 1995..Th1 cells have recently been shown to be regulated by Fas and we speculate that Fas-mediated mechanisms are involved in the regulation of both Th1 and T1 populations of T cells...
- Molecular genetic markers spanning mouse chromosome 10C A Kozak
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Genomics 8:519-24. 1990..genes involved in oncogenesis (Gli, Myb, Tra-1), proviral integration (Emv-25), and immune responses (Ifg, Ifgr, Pfp). The linkage map spans much of the chromosome and covers a region of the mouse genome with few molecular markers...
- Pathogenesis of herpes simplex virus type 1-induced corneal inflammation in perforin-deficient miceE Chang
Department of Molecular Microbiology Immunology, School of Medicine, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211, USA
J Virol 74:11832-40. 2000..There was no significant difference between the infectious viral titers isolated from the eyes of PKO and wild-type mice. Our findings show that perforin is important in the pathogenesis of HSK...
- TCR transgenic CD8+ T cells activated in the presence of TGFbeta express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejectionJudith A Kapp
Department of Ophthalmology, Spain Wallace Building, 619 South 19th Street, University of Alabama at Birmingham, Birmingham, AL 35233 7331, USA
Int Immunol 18:1549-62. 2006..These data show that TGFbeta-activated CD8+ T cells mediate antigen-specific, APC-focused patterns of suppression in vitro and in vivo...
- Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy beta-cells via the perforin and Fas pathwaysNadine L Dudek
St Vincent s Institute, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
Diabetes 55:2412-8. 2006..Therefore, NOD8.3 T-cells use both perforin and Fas pathways to kill beta-cells and the surprising blockade of NOD8.3 T-cell-mediated beta-cell death by SOCS-1 overexpression may be due in part to reduced target cell recognition...
- Cytotoxic T lymphocytes from cathepsin B-deficient mice survive normally in vitro and in vivo after encountering and killing target cellsKatherine Baran
Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrew s Place, East Melbourne 3002, Victoria, Australia
J Biol Chem 281:30485-91. 2006..We conclude that cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin...
- Protective immunity against secondary poxvirus infection is dependent on antibody but not on CD4 or CD8 T-cell functionVijay Panchanathan
Infection and Immunology Group, Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Mills Road, Acton, ACT 0200, Australia
J Virol 80:6333-8. 2006..Thus, antibody is essential, but CD4 or CD8 T cells are not required for recovery from secondary poxvirus infection...
- A role for perforin in activation-induced T cell death in vivo: increased expansion of allogeneic perforin-deficient T cells in SCID miceD Spaner
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada
J Immunol 162:1192-9. 1999..The results are compatible with a model of a defective activation-induced cell death (AICD) pathway, controlled by perforin, accounting for the increased expansion of alloreactive pko T cells...
- Restricted Semliki Forest virus replication in perforin and Fas-ligand double-deficient miceMohammed Alsharifi
Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia
J Gen Virol 89:1942-4. 2008..Although the mechanism responsible for this observation is yet to be established, the lower virus titres found in these mice indicate that the role of cytolytic effector molecules in antiviral immunity needs to be re-evaluated...
- Peroxynitrite-dependent killing of cancer cells and presentation of released tumor antigens by activated dendritic cellsJennifer Fraszczak
Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, Institut de Recherche Fédératif 100, Universite de Bourgogne, Dijon, France
J Immunol 184:1876-84. 2010....
- NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responsesPhilippe Krebs
Department of Genetics, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Blood 113:6593-602. 2009..We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development...
- Interferon-gamma prevents death of bystander neurons during CD8 T cell responses in the brainKirsten Richter
Department of Virology, University of Freiburg, Freiburg, Germany
Am J Pathol 174:1799-807. 2009....
- Hydrolysis of tumor cell lipids after CTL-mediated deathBryce Alves
Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV 89557, USA
Int Immunol 21:543-53. 2009..Also, CTL-mediated death caused as much FA release as death by disruption of cells by freeze-thawing. The released oleic acid may be sufficient to promote secondary apoptotic responses after CTL-induced trauma...
- Regulation of perforin lysis: implications for protein disulfide isomerase proteinsDavid L Tamang
Department of Microbiology and Immunology MS320, University of Nevada, School of Medicine, Reno, NV 89557, USA
Cell Immunol 255:82-92. 2009..Our results indicate that protein disulfide isomerases, in the ER or elsewhere, may protect T cells from their own perforin...
- The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cellsH Daniel Lacorazza
Laboratory of Molecular Aspects of Hematopoiesis, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Immunity 17:437-49. 2002..Our results uncover a specific role of MEF in the development and function of NK cells and in innate immunity...
- Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and BimThomas Kaufmann
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
Immunity 30:56-66. 2009..These observations identify caspase-8 and the BH3-only proteins Bid and Bim as potential therapeutic targets for treatment of inflammatory liver diseases...
- Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNFJ Schumann
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen Nurnberg, Germany
J Immunol 161:5745-54. 1998..These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals...
- CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumorsAngela M Tatum
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
J Immunol 181:4406-17. 2008..Finally, we show that production of IFN-gamma, but not perforin or TNF-alpha, by the donor lymphocytes is critical for control of autochthonous brain tumors...
- Dendritic cell apoptosis in the maintenance of immune toleranceMin Chen
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
Science 311:1160-4. 2006..The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance...
- CD8+ CTLs are essential for protective immunity against Encephalitozoon cuniculi infectionI A Khan
Departments ofMedicine and Microbiology and Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA
J Immunol 162:6086-91. 1999..This is the first report in which a strong dependence upon the cytolytic activity of host CD8+ T cells has been shown to be important in a parasite infection...
- Critical role for perforin-, Fas/FasL-, and TNFR1-mediated cytotoxic pathways in down-regulation of antigen-specific T cells during persistent viral infectionShenghua Zhou
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA
J Virol 76:829-40. 2002..As expression of the Bcl-2 family members controls susceptibility to apoptosis, this finding may provide a molecular basis for the survival of anergic cells under conditions of prolonged antigen stimulation...
- Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host diseaseYoshinobu Maeda
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Dr, Ann Arbor, MI 48109 0942, USA
Blood 105:2023-7. 2005..Together these results suggest that donor cdd CD8+ T cells expand continuously and cause lethal GVHD, and that both perforin and FasL are required for the contraction of allo-reactive CD8+ T cells...
- Interleukin-11 signaling is required for the differentiation of natural killer cells at the maternal-fetal interfaceRupasri Ain
Institute of Maternal Fetal Biology, Department of Pathology and Laboratory of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Dev Dyn 231:700-8. 2004..Thus, the defect in NK precursor cell maturation was not intrinsic to the NK precursor cells but was dependent upon the tissue environment. In summary, IL-11 signaling is required for decidual-specific maturation of NK cells...
- Perforin-dependent activation-induced cell death acts through caspase 3 but not through caspases 8 or 9Liane Chen
Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9
Eur J Immunol 33:769-78. 2003..Thus, perforin-dependent early AICD appears to require activation of caspase 3, but not caspases 8 or 9. As perforin has no intrinsic catalytic abilities, we propose that it releases some endogenous activity that can activate caspase 3...
- T-cells mediate an inhibitory effect of interleukin-4 on osteoclastogenesisDanijela Mirosavljevic
St Vincent s Institute of Medical Research, Fitzroy, Victoria, Australia
J Bone Miner Res 18:984-93. 2003....
- Perforin-mediated effector function within the central nervous system requires IFN-gamma-mediated MHC up-regulationCornelia C Bergmann
Department of Neurology, Keck School of Medicine, University of California, Los Angeles, CA 90033, USA
J Immunol 170:3204-13. 2003..The data further imply that IFN-gamma plays a crucial role in pathogenesis by regulating the balance between virus replication in oligodendrocytes, CD8(+) T cell effector function, and demyelination...
- Analysis of regulatory CD8 T cells in Qa-1-deficient miceDan Hu
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
Nat Immunol 5:516-23. 2004..These findings delineate a Qa-1-dependent T cell-T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease...
- Natural killer cells do not mediate facial motoneuron survival after facial nerve transectionSusanna C Byram
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA
Brain Behav Immun 17:417-25. 2003..Wild-type (WT), perforin/recombinase activating gene-2 knockout (pfp/RAG-2 KO), and common gamma-chain (gammac)/RAG-2 KO mice received a right facial nerve axotomy...
- Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbersKelly A Nordyke Messingham
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
J Immunol 171:4254-62. 2003..Thus, increasing the number of memory CD8(+) T cells can overcome diminished per-cell protective immunity in the absence of perforin...
- Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient miceVladimir P Badovinac
Department of Microbiology, University of Iowa, Iowa City 52242, USA
Immunity 18:463-74. 2003..Thus, perforin was essential for resistance to secondary LCMV infection, and, in the absence of perforin, vaccination resulted in lethal disease mediated by dysregulated CD8(+) T cell expansion and cytokine production...
- Perforin and Fas cytolytic pathways coordinately shape the selection and diversity of CD8+-T-cell escape variants of influenza virusGraeme E Price
Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, CB 2803, Augusta, Georgia 30912 3175, USA
J Virol 79:8545-59. 2005..We conclude that selection of viral CTL escape variants reflects coordinate action between the tightly controlled perforin/granzyme pathway and the more promiscuous Fas/FasL pathway...
- Lesions of T-cell-mediated kidney allograft rejection in mice do not require perforin or granzymes A and BPhilip F Halloran
Department of Medicine, Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Alberta, Canada
Am J Transplant 4:705-12. 2004..Together with previous graft survival studies, these results indicate that the granule-associated cytotoxic mechanisms of T cells are not the effectors of T-cell-mediated allograft rejection...
- Immunoproteasomes largely replace constitutive proteasomes during an antiviral and antibacterial immune response in the liverS Khan
Research Department and Institute for Pathology, Cantonal Hospital St Gallen, St Gallen, Switzerland
J Immunol 167:6859-68. 2001....
- Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanismBruce R Blazar
University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN 55455, USA
J Immunol 171:1272-7. 2003..These data indicate that PD-1 ligation down-regulates GVHD through modulation of IFN-gamma production and suggest a novel therapeutic target for inhibiting GVHD lethality...
- Activation-induced apoptosis of mature T cells is dependent upon the level of surface TCR but not on the presence of the CD3 zeta ITAMJ She
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Int Immunol 10:1733-40. 1998..Our data support the 'threshold model' of AICD by demonstrating that AICD is controlled by the strength of T cell activation...
- Loss of the perforin cytotoxic pathway predisposes mice to experimental cytomegalovirus retinitisRichard D Dix
Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
J Virol 77:3402-8. 2003....
- The regulation of tumor immunity by NKT cellsMark Smyth; Fiscal Year: 2007..This proposal focuses clearly on a pivotal immune control mechanism that will influence many current and future immunotherapies. ..
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2010..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2007..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSJerry Niederkorn; Fiscal Year: 2007..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2007....
- IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSJerry Niederkorn; Fiscal Year: 2006..All three of these aims will be addressed in a well-characterized mouse model of penetrating keratoplasty. ..
- IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSJerry Niederkorn; Fiscal Year: 2001..Both strategies procure antigen-specific suppression of host immune responses and should prove useful in preventing corneal graft rejection. ..
- In Situ Analysis of Hepatitis B virus-specific T cellsDorian McGavern; Fiscal Year: 2006..The main objective of this research is to more precisely define the contribution of HBV-specific CTL to viral clearance and pathogenesis by providing the first comprehensive analysis of these cells in situ. ..
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2006..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..
- B Cell Expansion After Dendritic Cell ImmunizationMichael Jordan; Fiscal Year: 2004..My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity. ..
- T cell Interactions in the CNS During Viral PersistenceDorian McGavern; Fiscal Year: 2005..The main objective of this research is to define the immunologic parameters that contribute to viral clearance versus persistence in the CNS and foster approaches that tip the balance in favor of clearance. ..
- IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSJerry Niederkorn; Fiscal Year: 2010..These studies will lead to improved strategies for re-establishing immune privilege of corneal transplants and offsetting the untoward effects of allergic diseases on the fate of corneal transplants. ..
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2010..This project will lead to better understanding of how cytotoxic function regulates the immune response and lead to improved therapies for patients with HLH and perhaps many other immunopathologic disorders. ..
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2010....
- An Animal Model of Hemophagocytic LymphohistiocytosisMichael Jordan; Fiscal Year: 2009
- IMMUNOLOGICAL MODULATION OF OCULAR TUMOR METASTASESJerry Niederkorn; Fiscal Year: 2010..The fourth aim will evaluate the therapeutic efficacy of a monoclonal antibody directed against human CD54 in controlling liver metastases in a nude mouse model of uveal melanoma. ..
- Mechanisms of neuronal injury during virus infection of the CNSCharles Howe; Fiscal Year: 2009..Importantly, we have found that treatment with an FDA-approved drug protects neurons and cognitive function without altering the ability of the immune system to clear the virus from the brain. ..
- Immune response to Pneumocystis and bone marrow failureNicole Meissner; Fiscal Year: 2009..Understanding how the immune system supports hematopoiesis is needed to develop strategies for the prevention and treatment of pancytopenia in AIDS patients. ..
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2009....
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 1993..The long range goals of this project are to understand immune regulatory processes in the eye and to manipulate such processes to reduce immune-mediated injury and corneal graft rejection...
- IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTSJerry Niederkorn; Fiscal Year: 1993..The results from these investigations should provide important insights into the immunobiology of corneal allografts and the feasibility of specific immunological strategies for promoting corneal allograft survival...
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2003..g., corneal transplantation). In some cases, it may be desirable to abrogate immune privilege to promote the immune-rejection of sight- and life-threatening ocular neoplasms. ..
- TRANSPLANT AND TUMOR REJECTION PROCESSES WITHIN THE EYEJerry Niederkorn; Fiscal Year: 2002..g., corneal transplantation) or abrogate immune privilege to protect against sight- and life-threatening neoplasms. ..